Asymmetric Synthesis of Chiral Phosphines, Arsines, and Stibines. There are now chiral phosphine-transition metal catalysts that rival enzymes in their efficiency for the asymmetric synthesis of important chiral drugs, fragrants, cosmetics, nutrients, vitamins, and pesticides. This project is aimed at a generalised asymmetric synthesis of the critical components of these enzyme mimics, notably enantiopure chiral phosphines, but also chiral arsines and stibines, by a highly innovative approach t ....Asymmetric Synthesis of Chiral Phosphines, Arsines, and Stibines. There are now chiral phosphine-transition metal catalysts that rival enzymes in their efficiency for the asymmetric synthesis of important chiral drugs, fragrants, cosmetics, nutrients, vitamins, and pesticides. This project is aimed at a generalised asymmetric synthesis of the critical components of these enzyme mimics, notably enantiopure chiral phosphines, but also chiral arsines and stibines, by a highly innovative approach that involves novel six-electron phosphenium, arsenium, and stibinium cations that are themselves stabilised by chiral phosphines so that chemical breeder reactions are possible. The use of chiral auxiliaries from the natural pool and from biotechnology will also be investigated.Read moreRead less
Quantum-chemical design of stereoregular polyphosphines for nanowires. In this project we will be designing and producing stereoregular polyphosphines that can self-assemble gold and silver complexes that mimic the molecular architectures of DNA and certain proteins. The longer gold complexes will behave as insulated nanowires, and are an exciting prospect for the development of nanotechnological devices. The shorter silver and gold complexes are expected to have significant antitumour propertie ....Quantum-chemical design of stereoregular polyphosphines for nanowires. In this project we will be designing and producing stereoregular polyphosphines that can self-assemble gold and silver complexes that mimic the molecular architectures of DNA and certain proteins. The longer gold complexes will behave as insulated nanowires, and are an exciting prospect for the development of nanotechnological devices. The shorter silver and gold complexes are expected to have significant antitumour properties. This project, which will use a unique theoretical-experimental approach to design the stereoregular polyphosphines, will enhance Australia's international scientific reputation, and will contribute to technological advancement in the national priority areas of nanotechnology and biotechnology.Read moreRead less
Towards Nano-circuits: 2 and 3-Dimensional Carbon-Wired Nano-architectures. Whilst Australia has a world-class profile in organotransition metal chemistry, main-group chemistry is under-represented, despite the enormous technological importance of materials based on these elements. In addition to the fundamental breakthrough science to be explored, the project will provide a training vehicle for 5 young scientists in both main group and organometallic chemistry. The target compounds involve an e ....Towards Nano-circuits: 2 and 3-Dimensional Carbon-Wired Nano-architectures. Whilst Australia has a world-class profile in organotransition metal chemistry, main-group chemistry is under-represented, despite the enormous technological importance of materials based on these elements. In addition to the fundamental breakthrough science to be explored, the project will provide a training vehicle for 5 young scientists in both main group and organometallic chemistry. The target compounds involve an essentially unique marriage of the fields of main-group and transition metal chemistry to provide complex nano-architectures based on the modular interconnection of metals and non-metals by carbon wires at the molecular level - nanoscopic counterparts of macroscopic circuit components.Read moreRead less
Heterobimetallic Coordination Complexes Containing Rare Earth and d-Block Ions. Rare earth compounds have major industrial applications such as MRI contrast agents and as catalysts within the rubber and petroleum industries. The fundamental knowledge ensuing from this project has the potential to produce new and advanced magnetic materials. Nanotechnological industries are being developed in Australia and this research will provide materials with the capacity to act as optical or electrical sw ....Heterobimetallic Coordination Complexes Containing Rare Earth and d-Block Ions. Rare earth compounds have major industrial applications such as MRI contrast agents and as catalysts within the rubber and petroleum industries. The fundamental knowledge ensuing from this project has the potential to produce new and advanced magnetic materials. Nanotechnological industries are being developed in Australia and this research will provide materials with the capacity to act as optical or electrical switches, magnetic storage devices or molecular sensors. This pioneering work will ensure that Australia remains at the forefront of chemical research within the rapidly advancing field of magnetochemistry.Read moreRead less
Understanding and Harnessing the Unique and Curious Metal Boron Bond: Unlocking the Metallaboratrane Cage. Metal-boron bonding holds enormous technological importance due to the emergence of boron-based metal-mediated synthetic transformations that access a diversity of high value-added fine chemicals. Whilst Australia boasts an emergent boron-based fine chemicals industry, no research program into the nature of metal boron bonding exists to provide either fundamental science or advanced trainin ....Understanding and Harnessing the Unique and Curious Metal Boron Bond: Unlocking the Metallaboratrane Cage. Metal-boron bonding holds enormous technological importance due to the emergence of boron-based metal-mediated synthetic transformations that access a diversity of high value-added fine chemicals. Whilst Australia boasts an emergent boron-based fine chemicals industry, no research program into the nature of metal boron bonding exists to provide either fundamental science or advanced training in organometallic boron chemistry. The proposed work offers two distinct national benefits: The maintenance of a discipline in which Australia leads the world (metallaboratranes) and the genesis of one, which whilst intensely studied elsewhere, is notably absent from the Australian science base (low coordinate, unsaturated boron chemistry).Read moreRead less
Dinuclear Ruthenium Complexes as Sequence- and Structure-Selective Binding Agents for DNA. Studies of the interaction of mononuclear metal complexes with DNA have greatly increased our understanding of the ways that small molecules recognise particular sites on DNA. However, in order to design drugs that target specific genes, and hence be potentially capable of controlling gene expression, it is necessary to study the binding of metal complexes that can associate with larger segments of DNA. ....Dinuclear Ruthenium Complexes as Sequence- and Structure-Selective Binding Agents for DNA. Studies of the interaction of mononuclear metal complexes with DNA have greatly increased our understanding of the ways that small molecules recognise particular sites on DNA. However, in order to design drugs that target specific genes, and hence be potentially capable of controlling gene expression, it is necessary to study the binding of metal complexes that can associate with larger segments of DNA. Using the combined expertise of the applicants, it is proposed to stereospecifically synthesise dinuclear complexes and study their DNA binding. This will greatly assist in the development of drugs that can selectively target genes and altered DNA.Read moreRead less
Mechanistic Studies on Biologically Active Iron Chelators. The need for orally effective drugs as alternatives to invasive treatment regimens such as subcutaneous infusion is an ongoing concern in health care. This is particularly true in people suffering iron overload. In many cases this condition is present at birth and thus the administration of vital iron chelation therapy via the oral route is a much preferred option. We have unearthed a novel series of candidates for iron chelation therapy ....Mechanistic Studies on Biologically Active Iron Chelators. The need for orally effective drugs as alternatives to invasive treatment regimens such as subcutaneous infusion is an ongoing concern in health care. This is particularly true in people suffering iron overload. In many cases this condition is present at birth and thus the administration of vital iron chelation therapy via the oral route is a much preferred option. We have unearthed a novel series of candidates for iron chelation therapy (the pyridine-2-carboxaldehyde isonicotinoyl hydrazone [PCIH] analogues) which show oral activity. These chelators undergo some interesting iron catalysed oxidation chemistry and it is vital that the mechanism of this reaction be elucidated to determine whether it will be of biological significance upon administration of these compounds as iron chelators.Read moreRead less
Spotlighting biologically active Iron (Fe) chelators within cells. Anti-cancer drugs that act in ways different from traditional chemotherapeutics offer hope in evading acquired drug resistance. Previously we have studied compounds that can enter cancer cells, bind iron and halt cellular proliferation. However, there are many sources of iron in cells and we do not know from where these iron chelators acquire their iron or how these iron complexes kill cancer cells. We will tackle this problem by ....Spotlighting biologically active Iron (Fe) chelators within cells. Anti-cancer drugs that act in ways different from traditional chemotherapeutics offer hope in evading acquired drug resistance. Previously we have studied compounds that can enter cancer cells, bind iron and halt cellular proliferation. However, there are many sources of iron in cells and we do not know from where these iron chelators acquire their iron or how these iron complexes kill cancer cells. We will tackle this problem by attaching light emitting probes to known iron chelators and mapping their location within cells with high resolution fluorescence microscopy. These experiments will spotlight the cellular location of these potential drugs bound to iron for the first time, providing crucial information on their mode of action.Read moreRead less
New Frontiers in Molybdenum Chemistry: Electronic Structure and Molybdoenzyme Function. Molybdenum enzymes play key roles in biology and environmental, biogeochemical and meteorological processes. This international, multidisciplinary project will employ advanced synthetic, instrumental and theoretical techniques to establish the link between electronic structures and molybdenum enzyme behaviour and function. The insights gained will inform the continuing development of agricultural, veterinary ....New Frontiers in Molybdenum Chemistry: Electronic Structure and Molybdoenzyme Function. Molybdenum enzymes play key roles in biology and environmental, biogeochemical and meteorological processes. This international, multidisciplinary project will employ advanced synthetic, instrumental and theoretical techniques to establish the link between electronic structures and molybdenum enzyme behaviour and function. The insights gained will inform the continuing development of agricultural, veterinary and medical treatments for diseases associated with enzyme dysfunction; these outcomes would be of enormous economic and societal benefit to Australia. The training of skilled scientists, access to advanced overseas facilities, and international recognition of Australian research, are important immediate benefits of the project.Read moreRead less
New Synthetic Routes to the Immobilisation of Mixed Valence Transition Metal Complexes on Conducting Metal Oxides. Highly coloured, electrochemically active transition metal dyes may find application electrochromic devices, where they may switch between contrasting coloured forms through a simple redox reaction. A prerequisite is that the dye be immobilised onto a solid conducting support whilst preserving the electrochemical and optical properties of the dye found in solution. This project tack ....New Synthetic Routes to the Immobilisation of Mixed Valence Transition Metal Complexes on Conducting Metal Oxides. Highly coloured, electrochemically active transition metal dyes may find application electrochromic devices, where they may switch between contrasting coloured forms through a simple redox reaction. A prerequisite is that the dye be immobilised onto a solid conducting support whilst preserving the electrochemical and optical properties of the dye found in solution. This project tackles this problem through a combination of organic and inorganic synthesis to develop new electrochromic dyes that may be attached to mesoporous titania.Read moreRead less